This is an application for a Mentored Research Scientist Development Award (K01). The goal of the proposed project is to provide the candidate with additional and advanced skills needed to establish an independent program of alcoholism research using clinical and neuroimaging methods. The candidate proposes a comprehensive training plan, combining didactic instruction overseen by his mentors, formal coursework, participation in applied training experiences with individual advisors, and participation in ongoing seminars. Training goals include: (1) gaining clinical and didactic training in alcoholism research, (2) receiving training in advanced neuroimaging methods and data analyses, and (3) training in the responsible conduct of research. The training plan will be executed in coordination with a proposed set of research studies. The research goal of this project is to reach a better understanding of structural and functional changes in the brains of subjects with alcohol use disorders (AUD subjects) during a fundamental form of learning, eyeblink classical conditioning, which has been widely used as a model system to study associative learning. It involves pairing two stimuli (tone and corneal airpuff) and, following repeated presentations, the subject learns the tone-airpuff relationship. While it has been shown that AUD subjects are impaired during this type of learning, remarkably little is known about the neural substrates of AUD subjects during this form of learning. The proposed research will characterize both structure and functional activity directly involved in eyeblink conditioning in an effort to better understand the neural bases underlying the learning deficits exhibited by AUD subjects. The studies will combine fMRI scanning during eyeblink conditioning with other advanced neuroimaging methods that will (1) assess baseline physiological states so that fundamental group differences in neurophysiology can be factored into data interpretation and (2) determine the integrity of white matter tracts that subserve the neural circuitry critical for eyeblink conditioning. The proposed application will identify neural mechanisms that contribute to the learning deficits as a function of alcohol abuse and, at the same time, enable the candidate to establish an independent research career in the study of alcoholism. This fundamental memory task is clinically relevant because it represents a foundation on which more complex learning is built, such as the consolidation of memory into long term storage. The application of this model system in AUD subjects would elucidate vulnerable neural structures that are uniquely recruited during basic learning processes. Findings from these projects will a) contribute to a more complete understanding of how alcohol affects memory and related brain structure and function;b) could lead to more effective diagnosis, prevention, and treatment of alcohol use disorders;and c) could help lead to more effective strategies for delivery of cognitive-based alcoholism interventions. PUBLIC HEALTH RELEVANCE: The goal of this research is to investigate how alcoholism affects brain structures critical for a fundamental form of memory, eyeblink classical conditioning. Findings from these projects will a) contribute to a more complete understanding of how alcohol affects memory and related brain structure and function;b) could lead to more effective diagnosis, prevention, and treatment of alcohol use disorders;and c) could help lead to more effective strategies for delivery of cognitive-based alcoholism interventions.